3065 Background: AG-014699 inhibits poly(ADP-ribose) polymerase (PARP) is a key enzyme in DNA repair. AG-014699 sensitizes cancer cells to DNA damaging drugs such as TMZ. AG-014699 is the first PARP inhibitor to be evaluated in cancer patients. Methods: In part 1 of the study, pts with solid tumors received AG-014699 + TMZ daily x 5 every 28 days. TMZ dose was half of standard (100 mg/m2 po) and AG-014699 (30 min infusion) was escalated up to the PARP-inhibitory dose (PID) as determined by PARP activity in peripheral blood lymphocytes (PBLs). We defined PID as maximal (at least >50%) reduction in PARP activity 24 hr after AG-014699. In part 2, AG-014699 dose was fixed at PID and TMZ was escalated to maximum tolerated dose or 200 mg/m2 in metastatic melanoma pts. Endpoints included safety, efficacy, PK and tumor PARP activity (obligatory in part 2). Overall objective based on xenograft data was to achieve > 40% PARP inhibition in tumor. Results: 27 pts enrolled, safety data available on first 18. In part 1...